Chlamydia trachomatis (CT) infection is the most prevalent bacterial sexually transmitted infection and causes major morbidity. Prevention and control measures have not diminished the epidemic, likely in part due to our lack of knowledge of factors influencing CT transmission, persistence, and recurrence could lead to improved or new CT control strategies. While presumably CT-specific immune responses contribute, we hypothesize that concomitant Trichomonas vaginalis (TV) infection and/or bacterial vaginosis (BV), both mucosal infections involving indole-producing organisms, contribute to CT persistence which facilitates transmission. The biological basis for this is that in vitro studies show that genital CT strains can utilize an indole-rescue mechanism to survive CT growth inhibitory effects of host IFN-. Supporting clinical evidence for the role of BV in CT transmission includes reports of association of BV with prevalent and incident CT infection and a trial by Schwebke et al. demonstrating asymptomatic BV treatment lowers incident CT infection risk. We also hypothesize that concomitant TV infection and/or BV delays CT clearance after therapy by the same mechanism, increasing the risk for CT persistence or recurrence. To address these hypotheses, we propose a prospective study in CRC Project 3 of CT-infected men and their female sexual partners evaluated at an STD clinic with an approach consisting of the following two specific aims: Aim 1: Evaluate the influence of concomitant TV infection and/or BV on CT concordance and CT organism load among CT-infected men and their female partners. Analyses will test for associations of concomitant TV infection and/or BV with CT concordance among CT-infected men and their female partners and magnitude of CT load at enrollment, adjusting for other factors that may influence these outcomes including demographics and host immune responses. Aim 2: Investigate the effect of concomitant TV infection and/or BV in CT-infected men and women on CT clearance after therapy and risk for persisting or recurrent CT infection. CT-infected men and women from the clinical core cohort are treated with azithromycin 1 g single dose and then they self-collect urogenital specimens and complete diaries both daily for 28 days post-therapy. Analyses will test for associations of concomitant TV infection and/or BV with delayed CT clearance post-therapy and persisting vs. recurrent CT infection at 28 days post-therapy, adjusting for demographics, behaviors, and host immune responses. Additional findings on the mucosal microbiome from Project 1 or on Gardnerella vaginalis virulence factors from Project 2 could provide further insight to findings from this Project 3. The broad, long-term objectives of the research is to improve our understanding of the factors, such as concomitant TV infection or BV, that influence CT transmission, persistence, and recurrence so that new or improved strategies can be developed for CT prevention and control.